Quade Cooper, Darcy Swain, Tom Banks and Allan Alaalatoa are all set to miss Saturday's clash at Brisbane's Suncorp Stadium, with only Alaalatoa likely to return the following week in Sydney.
Experienced and versatile, Reece Hodge has been called into the squad after Banks suffered a broken arm in the first Test win.
Hodge's best chance of selection may be on the bench, with Rennie likely to keep Andrew Kellaway at fullback after he was so impressive when switched from the wing following Banks' injury.
Likewise 22-year-old excitement machine Jordan Petaia should get that starting right wing role after his try-scoring effort coming off the bench.
It's also hard to see Rennie doing anything other than reward young playmaker Noah Lolesio with the five-eighth spot following his increasingly assured performance and perfect goalkicking after Cooper (calf) was ruled out just before kick off in Perth.
However, former Wallaby Drew Mitchell thinks the coach may opt for James O'Connor's experience.
"The language from Dave Rennie, saying that James O'Connor was … fit to play, but wasn't quite sharp enough, that to me might mean he's going to have more of a significant role at some point throughout the series," Mitchell told the Rugby Union Weekly podcast.
"Whether that means he goes straight back in at the No.10 jersey, Noah back to deputising role and maybe not having as much gametime as (last week) … I probably think they might go with James at No.10."
Swain will miss the rest of the series after his red card for a head butt following severe provocation was upheld by a Rugby World judicial committee, with the physical and energetic Matt Philip favourite to earn the start at lock after his showing from the bench.
Powerhouse prop Taniela Tupou is available for selection as he returns from a calf injury and it's well timed given Alaalatoa is unlikely to clear concussion protocols.
However Rennie has also used Tupou as a ball-running bench weapon in the past and he could also opt for the much-capped James Slipper to start.
Rennie's serene but thorough approach was lauded by assistant Matt Taylor on Wednesday, with the defence coach believing his calmness transfers to the team and that paid off when they were reduced to 14-men, and also suffering injuries early in the first Test.
"He (Rennie) is very measured, he doesn't get too high, he doesn't get too low," Taylor said.
"He takes things as it comes, so I certainly think that the osmosis of him being very calm probably promotes through the group.
"He's also very good at the clarity within the team. The fruit of that over the last couple of years maybe came out at the weekend, where we were able to adapt and adjust and get on with it without too much panic at all."
